MUSCULAR SYSTEM: Histology and Physiology

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MUSCULAR SYSTEM Histology and Physiology
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Introduction

• Types and Features of Muscle Tissue
• smooth muscle
• cardiac muscle
• muscle

skeletal
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• General Characteristics of Muscle
• contractility
• excitability

extensibility
elasticity
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General Functions of Muscle

• 1.
• 2.
• 3.
• 4.

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• Overview animation

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Skeletal Muscle Structure

• Skeletal muscles are composed of
  skeletal muscle fibers, connective tissue, blood
  vessels and nerves.

organs
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• Muscle fiber , is a skeletal muscle cell
• single, cylindrically shaped cell
• multiple nuclei, located peripherally
• development
• develop from
• myoblasts fuse to form muscle cells
• grow into skeletal
  muscle to form neuromuscular junction
• One neuron per skeletal muscle fiber
• numbers of striated muscle cells remains
  relatively constant after birth, but they may
  enlarge

myoblasts
Motor nerves
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• size of muscle fibers/cells
• 1 - 40 mm long
• 10 - 100 microns in diameter
• size of fibers varies with size of muscle
• muscle fibers are (banded
  appearance)

striated
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• Muscle Anatomy
• - plasma membrane of muscle
  cell

sarcolemma
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• endomysium
• also a delicate layer of CT with reticular fibers
• surrounds each muscle fiber outside the external
  lamina
• CT layer
• surrounds a bundle of muscle fibers,
  a

perimysium
muscle fasciculus
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epimysium

• a relatively thick layer of dense irreg.
  collagenous CT
• surrounds the many that make up
  a muscle
• covers the entire surface of the muscle

fasiculi
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• fascia
• a layer of fibrous CT outside the
• separates individual muscles
• may surround muscle groups
• fascia of an individual muscle is also called the
  epimysium

epimysium
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• these CT layers are continuous with each other
  and with the tendons and CT sheaths of the bones
• functions of CT
• holds muscles together
• provides a passageway to the muscle cells for
  blood vessels and nerves
• tendon or sheetlike aponeurosis
• epimysium fused to periosteum

indirect attachment
direct attachment
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• Muscle Fibers, Myofibrils, Myofilaments
• Muscle cell components
• sarcolemma

sarcoplasm
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• myofibrils
• threadlike structures, 1 - 3 micrometers in
  diameter
• extend from one end of the muscle fiber to
  another
• composed of protein myofilaments
• - thin filaments
• - thick filaments

actin
myosin
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• sarcomere
• a highly organized unit of myofilaments
• join end to end with other sarcomeres to form
  myofibrils
• extends from line
  (linedisc)
• Movie

Z line to Z
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• banding due to arrangements of actin myosin
  microfilaments
• light band
• includes a Z lines (disk)
• consists only of actin filaments
• extends on either side of Z line to myosin
  myofilaments

I (isotropic) band
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• A (anisotropic) band
• dark band
• extends the length of myosin myofilaments within
  the sarcomere

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• H zone
• a smaller band located within the center of each
  A-band
• only myosin myofilaments are present, no
  overlapping with actin

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• M line
• a dark band in the middle of the H zone
• consists of delicate filaments
  that attach to the center of the myosin
  myofilaments
• holds myosin myofilaments in place

(desmin)
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• titin (elastic filament)
• an elastic filament anchoring myosin myofilament
  at M line to Z disc
• resists excessive stretching or sarcomere

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• Actin myofilaments
• two strands of fibrous actin (F-actin) for double
  helix
• which are polymers of about 200 globular
  ( ) monomers

G-actin
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• two strands are arranged in a double helix
• each G-actin monomer has an
  to which myosin molecules
  can bind during muscle contraction

active site
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tropomyosin

• molecules
• an elongated molecule that winds along the groove
  of the F-actin double helix
• each molecule covers 7 G-actin active sites

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troponin

• composed of three subunits
• one with a high affinity for actin (TnI)
• one with a high affinity for tropomyosin (TnT)
• one with a high affinity for
  ions (TnC)
• spaced between ends of tropomyosin molecules in
  groove between F-actin double helix

calcium
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• in presence of Ca2, troponin is activated
• troponin activation results in it displacing
  tropomyosin deeper into the groove in F-actin
  double helix
• this exposes the actin active sites

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• Myosin myofilaments
• composed of elongated, club-shaped, myosin
  molecules
• two parts of myosin molecule
• rods (tails)
• with ATPase

heads
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• rod-like portions wound together
• about 100 myosin molecules per myosin myofilament
  
• point of attachment between head and rod is
  hinged
• myosin head forms cross bridge (contact) to
  actins active site

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• other
• A bands and I bands of parallel myofibrils are
  aligned to produce
  seen with a microscope
• many
• many glycogen granules lipid droplets

striated pattern
mitochondria
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• transverse (T) tubules
• tube like invaginations of the sarcolemma
• project into the muscle fiber and wrap around the
  sarcomeres where the actin and myosin
  microfilaments overlap
• lumen is continuous with exterior of muscle fiber
• filled with fluid

extracellular
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• sarcoplasmic reticulum
• highly specialized smooth ER
• near the T tubules, enlarged to form terminal
  cisternae
• is a T tubule and 2 terminal cisternae
• transports ions from
  sarcoplasm to its lumen

triad
calcium
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Clinical Focus

• Muscular dystrophy
• Muscular atrophy

Robbins
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Sliding Filament Theory

• Contracting Muscle
• actin and myosin myofilaments don't change length
  but slide past one another during muscle
  contraction.
• cross bridges form between heads of myosin and
  active sites on actin, release, and then reform,
  causing the actin myofilaments at each end of the
  sarcomere to slide past the myosin microfilaments
  toward the H zone
• I bands and H zones become more narrow during
  contraction H zone may disappear
• A bands remain constant in length
• sarcomere shortens

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• Fig. 9.6

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• Slidng filament theory 1
• Slidng filament theory 2

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Neuromuscular Junctions

• Motor neurons
• specialized nerve cells that propagate action
  potentials to skeletal muscle fibers at a
  relatively high velocity
• most motor neurons enter skeletal muscles with
  the blood vessels branching when they reach the
• each motor neuron innervates more than muscle
  fiber
• a branch of the motor neuron
  innervates one muscle fiber, forming a
  neuromuscular junction or synapse near the center
  of the muscle fiber

perimysium
single
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• Neuromuscular junction structure
• presynaptic (axonal) terminal
• postsynaptic terminal (motor end plate)
• synaptic cleft
• synaptic vesicles

Release acetylcholine
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Quick Review

• Membrane Transport 2
• Active processes
• Move substances uphill or against their
  concentration gradient most often is
  the energizer for this process
• Active Transport is the mechanism
• an
  mechanism

ATP
Na - K ATPase
antiport
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• Na - K ATPase 1
• Na - K ATPase 2

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Resting Membrane Potential

• The cell membrane is more permeable to some
  molecules than to others.
• Membrane Potentials
• A , or electrical potential due to the
  separation of charges by the cell membrane.
• Resting Membrane Potential occur in all cells due
  to
• RMP ranges from -20 to -200 millivolts (mV)
• state of the cell

Voltage
Concentration Gradients
Active Transport Pumps
Electrical Gradients
Polarized
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• Inside of the cell is electrically neutral
• Outside of the cell is electrically neutral
• But,
• higher outside of cell
• Membrane impermeable to Na
• higher inside of cell
• Membrane permeable to K
• K diffuses down its concentration gradient
• This concentration difference make a loss of
  positive charges inside the cell
• maintains this imbalance How?

Na
K
Na - K ATPase
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• But there is more,
• reinforce the
  ion concentration on the inside and outside of
  the cell
• Electrical forces resist K diffusion out of the
  cell
• An produces the RMP

Electric charges
electrochemical gradient
Fig. 9.7
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• Action Potential tracing
• Stimulus
• Na channel open -gt Na influx
• K channel begin to open late in phase
• Na channel close
• K channel open
• (after
  potential)
• K leaks until Na-K ATPase
  reestablish RMP

Depolarization phase
Repolarization phase
Hyperpolarization
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Regulation - Skeletal Muscle Fiber

• Regulation of Contraction
• Nerve Stimulus Neuromuscular Junction
• has cell body in
  CNS (brain spinal cord)

Motor neuron
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Action potential

• generated at
  cell body travels along axon
• Axon branch to muscle fiber
• Muscle fiber innervated by one motor neuron
• is a motor neuron and
  all muscle fibers it stimulates
• fine muscle control -gtfew fibers/unit
• coarse movement -gtmay fibers/unit

Motor unit
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• Neuromuscular junction formed by axonal terminal
  and muscle fiber (motor end plate)
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  (presynaptic membrane)
• Synaptic vesicles -gt
• Synaptic cleft
• Junctional folds of sacrolemma (post synaptic
  membrane)
• ACh receptors

Axonal terminal
acetylcholine (ACh)
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• Nerve AP
• Nerve AP arrives at the presynaptic terminal
  causing voltage-gated Ca2 ion channels to open
• Ca2 influx -gt
  into synaptic cleft
• diffusion of ACh across synaptic cleft
• Movie

exocytosis of ACh
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• Muscle fiber AP
• 2-ACh binds chemically gated ACh receptor-channel
• opens ACh receptor-channel -gt Na influx -gt
  of sacrolemma
• graded potential across sarcolemma

depolarization
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• Propagation of AP
• channels
  open -gt AP propagation
• ACh in synaptic cleft broken down by
  (AChE)
• acetic acid -gtbroken down by cells
• choline -gtuptake into axon terminal
  reincorporated into ACh

Voltage-gated Na
acetylcholinesterase
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• Excitation-Contraction Coupling
• Muscle fiber causes muscle fiber
  contraction
• AP propagated along the sarcolemma, causes
  wave to spread along the
  sarcolemma of the T tubules
• Depolarization of the T tubule membrane
• triggers opening of voltage-gated Ca2 channels
  to open in sarcoplasmic reticulum
• Ca2 influx into sarcoplasm from sarcoplasmic
  reticulum
• Movie

AP
depolarization
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• Repolarization restores the polarized state
• voltage-gated Na channels close
• voltage-gated K channels open
• Na - K pump restores electrochemical gradient

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• sarcoplasmic Ca2 binds (TnC)
• activated troponin moves deeper into the
  F-actin groove, and exposes G-actin active sites
• G-actin active site exposure allows cross-bridge
  attachment of myosin head

troponin
tropomyosin
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Contraction Skeletal Muscle Fiber

• Sliding Filament Mechanism of Contraction
• Myosin myofilament head has
  hydrolyzed ATP -gt ADP P (that remain attached)
• energy transfer cocks myosin (energizes) head

ATPase
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• Myosin head attaches to a active
  site
• Cross bridge formed
• phosphate is released
• ADP may remain attached to myosin head

G-actin
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• Energized myosin head bends pulls on the
  actin myofilament
• Actin stroked past myosin myofilament
• ADP released from de-energized head
• myosin head remains fixed to actins active site

power stroke
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• Myosin myofilament head ATPase hydrolyze ATP -gt
  ADP P (that remain attached)
• myosin head from actins active site
• energy transfer cocks myosin (energizes) head
• Mechanism repeats

released
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• Movie1
• Movie2
• Movie3

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• Sliding Filament Mechanism Questions
• Do actin myofilaments change in overall length?
• Do myosin myofilaments change in overall length?
• What are the structures that form a cross-bridge?
  
• How many times can cross-bridges be formed during
  one muscle fiber contraction?
• Which myofilaments are stationary (fixed), and
  which myofilaments move during a muscle fiber
  contraction?
• Describe the appearance of the banding in a
  relaxed muscle fiber?
• During a muscle fiber contraction, how does the
  appearance of the H-zone change?
• During a muscle fiber contraction, how does the
  appearance of the A-band change?
• During a muscle fiber contraction, how does the
  appearance of the I-band change?
• During a muscle fiber contraction, how does the
  appearance of the Z-discs change?
• During a muscle fiber contraction, how does the
  appearance of the sarcomere change?
• How does this relate to motor unit size and the
  amount of fine or coarse control over muscle
  movement?

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• All-or-None Principle
• An action potential (AP) is all-or-none.
• depolarization
  occurs
• insufficient cation influx will not trigger
  opening of voltage-gated cation channels
• a local depolarization, but no propagation (AP)
• threshold, a membrane potential at which an AP is
  produced as a result of depolarization, is not
  reached
• NONE no AP -gt no muscle fiber contraction
• depolarization occurs
• Cation influx trigger opening of voltage-gated
  cation channels
• threshold is reached, an AP is propagated
• ALL AP -gt muscle fiber contraction
• A stronger-than-threshold stimulus produces an AP
  of the same magnitude -gt therefore produces an
  identical contraction

Subthreshold
Threshold
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• Fig. 11.22
• Refractory Period
• early in AP
• NO additional stimulus will generate another AP
• Refractory Period
• following abs. ref. p., late repolarization
  phase, many open K channels causes
  hyperpolarization
• only a stronger-than-threshold stimulus can
  initiate another AP

Absolute
Relative
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• The Muscle Twitch and Development of Muscle
  Tension
• A single AP causes a brief muscle fiber
  contraction followed by relaxation
• Contraction -gt tension -gt transferred to CT -gt
  movement

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• Graded Muscle Responses
• Myogram is tracing of a muscle contraction, not
  an AP
• Latent (lag) phase
• delay betw. AP, depolarization, start of
  mechanical events
• mechanical events of contraction
• tension generated
• Relaxation phase
• cell repolarization to polarized state
• tension decreases

Contraction phase
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• Multiple Motor Unit Summation
• Each motor unit responds in an All-or-None
  fashion
• A whole muscle is capable of producing an
  increasing amount of tension as the number of
  
  stimulated increases
• Recruitment of motor units
• threshold stimulus -gt 1st muscle fiber
  contractions few motor units
• maximal stimulus -gt all motor units recruited

motor units
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• Multiple Wave Summation
• AP frequency increasing (slowly)
• Muscle tension increases Why?

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• Tetanus
• AP frequency increasing (rapidly)
• Muscle tension increases Why?
• Incomplete tetany vs. Complete tetany

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• Treppe The Staircase Effect
• Maximal stimulus at a (low and constant)
  frequency that allow for complete relaxation
  between stimuli
• second contraction produces greater tension than
  the first, and the third contraction greater
  tension than the second

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• Muscle Tone
• Relatively constant tension produced by a muscle
  for long periods as a result of asynchronous
  contraction of motor units
• Types of Contraction
• Isometric contractions
• contractions
• Concentric contractions
• Eccentric contractions

Isotonic
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• Isometric and/Isotonic contraction

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• Length-Tension Relationship
• muscle not stretched
• tension produced is
• muscle is severely stretched
• tension produced is
• optimally stretched
• tension produced is maximal
• number of cross-bridges that can form is maximal

small
small
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• Length-Tension Relationship

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Muscle Metabolism

• Providing Energy for Muscle Contraction
• Stored ATP
• 4-6 seconds
• Direct Phosphorylation of ADP by Creatine
  Phosphate
• 15 seconds
• 1 ATP/CP
• Anaerobic Glycolysis and Lactic Acid Formation
• 30-60 seconds
• 2 ATP/glucose or lactic acid
• Aerobic Respiration
• Hours
• 36 ATP/glucose

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• Oxygen Debt
• Which pathway for ATP regeneration requires
  oxygen?
• Lactic acid buildup, ATP CP store depletion
  result in -gt
• Oxygen debt is the time required for the body to
  remove lactic acid and regenerate ATP CP stores
• How? Increased

oxygen debt
breathing
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• Fatigue
• Muscle fatigue
• relative deficit of
• lactic acid accumulation (pain) and
• ion loss in sweat
• Na - K pump less efficient
• contracture results Why?
• Psychological fatigue
• the flesh (muscle) is still willing, but the
  spirit is not!
• Heat Production During Muscle Activity
• 40 waste energy in the form of heat is
  generated by muscles

ATP
ion imbalances
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• Velocity and Duration of Contraction
• Muscle Fiber Type
• Slow oxidative fibers
• Fast oxidative fibers
• Fast glycolytic fibers
• For each fiber type
• What is the primary pathway for ATP synthesis?
• What is the relative myglobin content? Why?
• What is the fibers relative color? Why?
• What is the relative amount of mitochondria?
• What is the relative concentration of
  capillaries?
• What is the relative rate of fatigue?
• What is the relative speed of fiber contract?
• What type of activity is the each fiber best
  suited?

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General Principles

• Tendons Attach muscles to bones
• Aponeurosis A very broad tendon
• Muscles
• Origin or head Muscle end attached to more
  stationary of two bones
• Insertion Muscle end attached to bone with
  greatest movement
• Belly Largest portion of the muscle between
  origin and insertion

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• Synergists Muscles that work together to cause a
  movement
• Prime mover Plays major role in accomplishing
  movement
• Agonist Muscle causing an action when contracts
• Antagonist A muscle working in opposition to
  agonist

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• Antagonist muscle pair

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• Fixators Stabilize joint/s crossed by the prime
  mover
• Muscle shapes
• unipinnate bipinnate multipinnate
• parallel circular
• convergent
• quadraangular trapazoidal triangular
  rhomboidal fusiform
• digastric bicipital

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Muscle Shapes
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Nomenclature

• Muscles are named according to
• Location pectoralis gluteus, brachial
• Size maximus, minimus, longus, brevis
• Shape deltoid, quadratus, teres
• Orientation rectus
• Origin and insertion sternocleidomastoid,
  brachioradialis
• Number of heads biceps, triceps
• Function abductor, adductor, masseter

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Muscle Movements

• Muscle contractions are a pull or force by
  relative positions of
• Lever Rigid shaft or bone
• Fulcrum Pivot point or joint
• Weight or resistance

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Classes of Levers

• Class I
• Fulcrum between force and weight
• Seesaw or head movement
• Class II
• Weight is between fulcrum and pull
• Wheelbarrow, standing on toes
• Class III
• Pull located between fulcrum and weight
• Person using a shovel
• Most common

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Assignments

• Explain the events that influence the width of
  each band of a sarcomere when a muscle goes
  through the sequence of stretching, contracting,
  and then relaxing.
• Describe and compare the three types of muscle
  tissue (skeletal, cardiac, smooth) on the basis
  of their microscopic structure, location,
  function, and innervation.
• What is the difference between a strain and a
  sprain?
• Describe the sliding filament mechanism (theory)
  of muscle contraction.

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Smooth MuscleThis may be covered only in part
or not at all.

• Arrangement and Microscopic Structure of Smooth
  Muscle Fibers
• Basic Characteristics
• Shape?
• Nucleus?
• Striations?
• Sarcomeres?
• CT coverings?
• SR?
• sheets

Layered
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• Filaments Sarcolemma
• Intermediate fibers connect to
  imbedded in the sarcolemma
• Transfer tension of myofilaments to sarcolemma
  and endomysium
• No
• many F-actin filaments
• few Myosin myofilaments
• (small pockets), no T tubule

dense bodies
troponin
caveoli
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• Contraction of Smooth Muscle
• Regulation of Contraction
• regulation
• Spontaneous depolarization due to local stimulus
• Pacemaker cells communicate stimulus via gap
  junctions
• nervous system branches
• Diffuse synaptic junctions -gt ACh released
• regulation
• Hormones

Local
Autonomic
Endocrine
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• Mechanism and Characteristics of Contraction
• Stimulus -gt local, ANS, hormone -gt AP
• Ca2 channel opens in sarcolemma
• Ca2 binds -gt activates
• Activated calmodulin binds myosin kinase -gt
  activates
• Activated
  transfer phosphate from ATP to myosin head -gt
  activates
• Cycle of cross-bridge formation, movement,
  detachment, and cross-bridge formation occurs
• Relaxation occurs when
  removes phosphate from myosin

calmodulin
myosin kinase
myosin phosphatase
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• Special Features of Smooth Muscle Contraction
• Basic Features
• Slow, prolonged contractions
• Peristalsis
• Low energy requirement
• Response to Stretch
• Stretch -gt can increase contraction -gt increase
  tension
• Hyperplasia

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• Types of Smooth Muscle
• Smooth Muscle (visceral
  muscle)
• Contracts as a unit and rhythmically
• gap junctions
• Spontaneous AP
• local control mechanisms
• Smooth Muscle
• Muscle fiber must be stimulated (ANS)
• few gap junctions

Single-Unit
Multiunit
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Fig. 9.8
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Fig. 9.9
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MUSCULAR SYSTEM Muscle Physiology Stuff